This study will analyze the sequence of structural changes, including ultrastructure, occurring in hearts subjected to chronic work overload which results in cardiac hypertrophy and correlate these changes with alterations in regional myocardial blood flow distribution and regional myocardial function. Pressure overload will be induced by aortic constriction with a cuff or DOCA induced hypertension and volume overload will be caused by an arteriovenous fistula regulated by a cuff. These work overloads will be caused by an arteriovenous fistula regulated by a cuff. These work overloads will be induced in chronically instrumented conscious pigs. Regional myocardial blood flow will be measured using radiolabeled tracer microsphere methods. Regional myocardial function will be determined by ultrasonic dimension gauges. We will study the animals in the early stage of uncompensated work overload when cardiac failure occurs. We will also determine the limits of coronary vascular capacity or coronary reserve in these hearts by measuring coronary flow at maximal vasodilation induced by adenosine or excercise. At autopsy, using quantitative morphometric techniques, we will determine the sequence of structural changes, including ultrastructural and vascular changes, occurring in these hearts and correlate them with the functional alterations. We will attempt to define the factors that characterize early irreversibility of cardiac hypertrophy. Clearly defining these changes and the factors that influence them may help determine appropriate clinical therapy for patients with hypertrophic heart disease.